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Wiley Interdisciplinary Reviews. Systems Biology and Medicine

Matteo Ottolini, Kwangseok Hong, Swapnil K Sonkusare
Small arteries in the body control vascular resistance, and therefore, blood pressure and blood flow. Endothelial and smooth muscle cells in the arterial walls respond to various stimuli by altering the vascular resistance on a moment to moment basis. Smooth muscle cells can directly influence arterial diameter by contracting or relaxing, whereas endothelial cells that line the inner walls of the arteries modulate the contractile state of surrounding smooth muscle cells. Cytosolic calcium is a key driver of endothelial and smooth muscle cell functions...
March 18, 2019: Wiley Interdisciplinary Reviews. Systems Biology and Medicine
Subhasish Baral, Rubesh Raja, Pramita Sen, Narendra M Dixit
The CD8+ T cell response is critical to the control of viral infections. Yet, defining the CD8+ T cell response to viral infections quantitatively has been a challenge. Following antigen recognition, which triggers an intracellular signaling cascade, CD8+ T cells can differentiate into effector cells, which proliferate rapidly and destroy infected cells. When the infection is cleared, they leave behind memory cells for quick recall following a second challenge. If the infection persists, the cells may become exhausted, retaining minimal control of the infection while preventing severe immunopathology...
February 27, 2019: Wiley Interdisciplinary Reviews. Systems Biology and Medicine
Benjamin Croop, Chenyi Zhang, Youngbin Lim, Ryan M Gelfand, Kyu Young Han
Recent advances in single-molecule techniques have led to new discoveries in analytical chemistry, biophysics, and medicine. Understanding the structure and behavior of single biomolecules provides a wealth of information compared to studying large ensembles. However, developing single-molecule techniques is challenging and requires advances in optics, engineering, biology, and chemistry. In this paper, we will review the state of the art in single-molecule applications with a focus over the last few years of development...
February 6, 2019: Wiley Interdisciplinary Reviews. Systems Biology and Medicine
Inez Lam, Christina M Pickering, Feilim Mac Gabhann
Receptor tyrosine kinases (RTKs) are cell membrane proteins that provide cells with the ability to sense proteins in their environments. Many RTKs are essential to development and organ growth. Derangement of RTKs-by mutation or by overexpression-is central to several developmental and adult disorders including cancer, short stature, and vascular pathologies. The mechanism of action of RTKs is complex and is regulated by contextual components, including the existence of multiple competing ligands and receptors in many families, the intracellular location of the RTK, the dynamic and cell-specific coexpression of other RTKs, and the commonality of downstream signaling pathways...
March 2019: Wiley Interdisciplinary Reviews. Systems Biology and Medicine
Haihan Tan, Wee-Wei Tee
The germ line is a crucial cell lineage that is distinct from somatic cells, and solely responsible for the trans-generational transmission of hereditary information in metazoan sexual reproduction. Primordial germ cells (PGCs)-the precursors to functional germ cells-are among the first cell types to be allocated in embryonic development, and this lineage commitment is a critical event in partitioning germ line and somatic tissues. Classically, mammalian PGC development has been largely informed by investigations on mouse embryos and embryonic stem cells...
January 2019: Wiley Interdisciplinary Reviews. Systems Biology and Medicine
Andrea Esposito, Carlo Annunziatella, Simona Bianco, Andrea M Chiariello, Luca Fiorillo, Mario Nicodemi
The depth and complexity of data now available on chromosome 3D architecture, derived by new technologies such as Hi-C, have triggered the development of models based on polymer physics to explain the observed patterns and the underlying molecular folding mechanisms. Here, we give an overview of some of the ideas and models from physics introduced to date, along with their progresses and limitations in the description of experimental data. In particular, we focus on the Strings&Binders and the Loop Extrusion model of chromatin architecture...
December 19, 2018: Wiley Interdisciplinary Reviews. Systems Biology and Medicine
Emidio Capriotti, Kivilcim Ozturk, Hannah Carter
More reliable and cheaper sequencing technologies have revealed the vast mutational landscapes characteristic of many phenotypes. The analysis of such genetic variants has led to successful identification of altered proteins underlying many Mendelian disorders. Nevertheless the simple one-variant one-phenotype model valid for many monogenic diseases does not capture the complexity of polygenic traits and disorders. Although experimental and computational approaches have improved detection of functionally deleterious variants and important interactions between gene products, the development of comprehensive models relating genotype and phenotypes remains a challenge in the field of genomic medicine...
December 12, 2018: Wiley Interdisciplinary Reviews. Systems Biology and Medicine
Nicole A Szydlowski, Jane S Go, Ying S Hu
Synergistic developments in advanced fluorescent imaging and labeling techniques enable direct visualization of the chromatin structure and dynamics at the nanoscale level and in live cells. Super-resolution imaging encompasses a class of constantly evolving techniques that break the diffraction limit of fluorescence microscopy. Structured illumination microscopy provides a twofold resolution improvement and can readily achieve live multicolor imaging using conventional fluorophores. Single-molecule localization microscopy increases the spatial resolution by approximately 10-fold at the expense of slower acquisition speed...
November 19, 2018: Wiley Interdisciplinary Reviews. Systems Biology and Medicine
Michael I Miller, Sylvain Arguillère, Daniel J Tward, Laurent Younes
The nonlinear systems models of computational anatomy that have emerged over the past several decades are a synthesis of three significant areas of computational science and biological modeling. First is the algebraic model of biological shape as a Riemannian orbit, a set of objects under diffeomorphic action. Second is the embedding of anatomical shapes into the soft condensed matter physics continuum via the extension of the Euler equations to geodesic, smooth flows with inverses, encoding divergence for the compressibility of atrophy and expansion of growth...
November 2018: Wiley Interdisciplinary Reviews. Systems Biology and Medicine
H Frederik Nijhout, Janet A Best, Michael C Reed
All organisms are subject to large amounts of genetic and environmental variation and have evolved mechanisms that allow them to function well in spite of these challenges. This property is generally referred to as robustness. We start with the premise that phenotypes arise from dynamical systems and are therefore system properties. Phenotypes occur at all levels of the biological organizational hierarchy, from gene products, to biochemical pathways, to cells, tissues, organs, appendages, and whole bodies. Phenotypes at all these levels are subject to environmental and genetic challenges against which their form and function need to be protected...
October 29, 2018: Wiley Interdisciplinary Reviews. Systems Biology and Medicine
Ameneh Asgari-Targhi, Elizabeth B Klerman
Circadian rhythms are endogenous ~24-hr oscillations usually entrained to daily environmental cycles of light/dark. Many biological processes and physiological functions including mammalian body temperature, the cell cycle, sleep/wake cycles, neurobehavioral performance, and a wide range of diseases including metabolic, cardiovascular, and psychiatric disorders are impacted by these rhythms. Circadian clocks are present within individual cells and at tissue and organismal levels as emergent properties from the interaction of cellular oscillators...
October 17, 2018: Wiley Interdisciplinary Reviews. Systems Biology and Medicine
Ghee Chuan Lai, Tze Guan Tan, Norman Pavelka
Mammalian barrier surfaces are densely populated by symbiont fungi in much the same way the former are colonized by symbiont bacteria. The fungal microbiota, otherwise known as the mycobiota, is increasingly recognized as a critical player in the maintenance of health and homeostasis of the host. Here we discuss the impact of the mycobiota on host physiology and disease, the factors influencing mycobiota composition, and the current technologies used for identifying symbiont fungal species. Understanding the tripartite interactions among the host, mycobiota, and other members of the microbiota, will help to guide the development of novel prevention and therapeutic strategies for a variety of human diseases...
September 25, 2018: Wiley Interdisciplinary Reviews. Systems Biology and Medicine
Dejun Lin, Giancarlo Bonora, Galip Gürkan Yardımcı, William S Noble
Recent advances in chromosome conformation capture technologies have led to the discovery of previously unappreciated structural features of chromatin. Computational analysis has been critical in detecting these features and thereby helping to uncover the building blocks of genome architecture. Algorithms are being developed to integrate these architectural features to construct better three-dimensional (3D) models of the genome. These computational methods have revealed the importance of 3D genome organization to essential biological processes...
July 18, 2018: Wiley Interdisciplinary Reviews. Systems Biology and Medicine
Stefano Morotti, Eleonora Grandi
Quantitative systems modeling aims to integrate knowledge in different research areas with models describing biological mechanisms and dynamics to gain a better understanding of complex clinical syndromes. Heart failure (HF) is a chronic complex cardiac disease that results from structural or functional disorders impairing the ability of the ventricle to fill with or eject blood. Highly interactive and dynamic changes in mechanical, structural, neurohumoral, metabolic, and electrophysiological properties collectively predispose the failing heart to cardiac arrhythmias, which are responsible for about a half of HF deaths...
July 17, 2018: Wiley Interdisciplinary Reviews. Systems Biology and Medicine
Evan Tsiklidis, Carrie Sims, Talid Sinno, Scott L Diamond
Trauma with hypovolemic shock is an extreme pathological state that challenges the body to maintain blood pressure and oxygenation in the face of hemorrhagic blood loss. In conjunction with surgical actions and transfusion therapy, survival requires the patient's blood to maintain hemostasis to stop bleeding. The physics of the problem are multiscale: (a) the systemic circulation sets the global blood pressure in response to blood loss and resuscitation therapy, (b) local tissue perfusion is altered by localized vasoregulatory mechanisms and bleeding, and (c) altered blood and vessel biology resulting from the trauma as well as local hemodynamics control the assembly of clotting components at the site of injury...
July 2018: Wiley Interdisciplinary Reviews. Systems Biology and Medicine
Magdalena Harakalova, Folkert W Asselbergs
Dilated cardiomyopathy (DCM) is a form of severe failure of cardiac muscle caused by a long list of etiologies ranging from myocardial infarction, DNA mutations in cardiac genes, to toxics. Systems analysis integrating next-generation sequencing (NGS)-based omics approaches, such as the sequencing of DNA, RNA, and chromatin, provide valuable insights into DCM mechanisms. The outcome and interpretation of NGS methods can be affected by the localization of cardiac biopsy, level of tissue degradation, and variable ratios of different cell populations, especially in the presence of fibrosis...
July 2018: Wiley Interdisciplinary Reviews. Systems Biology and Medicine
Julia M Barbarino, Michelle Whirl-Carrillo, Russ B Altman, Teri E Klein
As precision medicine becomes increasingly relevant in healthcare, the field of pharmacogenomics (PGx) also continues to gain prominence in the clinical setting. Leading institutions have begun to implement PGx testing and the amount of published PGx literature increases yearly. The Pharmacogenomics Knowledgebase (PharmGKB; is one of the foremost worldwide resources for PGx knowledge, and the organization has been adapting and refocusing its mission along with the current revolution in genomic medicine...
July 2018: Wiley Interdisciplinary Reviews. Systems Biology and Medicine
Kevin R Costello, Dustin E Schones
Metabolic diseases such as obesity and diabetes are complex diseases resulting from multiple genetic and environmental factors, such as diet and activity levels. These factors are well known contributors to the development of metabolic diseases. One manner by which environmental factors can influence metabolic disease progression is through modifications to chromatin. These modifications can lead to altered gene regulatory programs, which alters disease risk. Furthermore, there is evidence that parents exposed to environmental factors can influence the metabolic health of offspring, especially if exposures are during intrauterine growth periods...
July 2018: Wiley Interdisciplinary Reviews. Systems Biology and Medicine
Makiko Iwafuchi-Doi
Pioneer transcription factors play a primary role in establishing competence for gene expression and initiating cellular programming and reprogramming, and their dysregulation causes severe effects on human health, such as promoting tumorigenesis. Although more than 200 transcription factors are expressed in each cell type, only a small number of transcription factors are necessary to elicit dramatic cell-fate changes in embryonic development and cell-fate conversion. Among these key transcription factors, a subset called "pioneer transcription factors" have a remarkable ability to target nucleosomal DNA, or closed chromatin, early in development, often leading to the local opening of chromatin, thereby establishing competence for gene expression...
June 27, 2018: Wiley Interdisciplinary Reviews. Systems Biology and Medicine
Xu Lan, Martha S Field, Patrick J Stover
Folate-mediated one-carbon metabolism (FOCM) comprises a network of interconnected folate-dependent metabolic pathways responsible for serine and glycine interconversion, de novo purine synthesis, de novo thymidylate synthesis and homocysteine remethylation to methionine. These pathways are compartmentalized in the cytosol, nucleus and mitochondria. Individual enzymes within the FOCM network compete for folate cofactors because intracellular folate concentrations are limiting. Although there are feedback mechanisms that regulate the partitioning of folate cofactors among the folate-dependent pathways, less recognized is the impact of cell cycle regulation on FOCM...
June 11, 2018: Wiley Interdisciplinary Reviews. Systems Biology and Medicine
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